Out of fashion plants at the “big data” Era: Illuminating the overlooked Apocynaceae alkaloids chemical space by Molecular Networking

The latest advances in bio-informatics and analytical chemistry, particularly in mass spectrometry, are totally revolutionizing the field of natural product discovery [1]. Indeed, when experimental data are combined to computational algorithms, a powerful synergy arises and enables to expedite the discovery process by predicting the structural identity of all detectable metabolites within complex natural extracts [2].

Despite the fact that Apocynaceae plants were extensively studied since the beginning of phytochemistry in the 50's due to their content in alkaloids with major pharmacological activities, a thorough literature survey reveals that a considerable number of those early obtained compounds, has remained without biological evaluation neither assigned structure. Obviously, this is understandable given the striking molecular architecture complexity of those compounds. In this vein, as part of our continuing interest for monoterpenoid indole alkaloid chemistry [3], we decided to chemically reinvestigate the previously studied Apocynaceae plant, Picralima nitida, using molecular networking as a dereplication strategy [4]. By taking advantage from our historical laboratory's collections of natural monoterpenoid indole alkaloids, we used the above mentioned natural standards to seed the alkaloidic extract networks, in order to shed light on unexplored matter leading to prioritize the isolation workflow towards unknown compounds. Additionally, as the training set of natural standards possesses characterized biological attributes, their integration provided an early biological annotation of the networks. Satisfyingly, this study led to the identification of new compounds bearing unprecedented carbon skeleton and interesting biological activities. This presentation is intended to offer the promising perspectives gleaned from the reinvestigation of several forgotten plants by this new generation of sophisticated tools.

Acknowledgements: We are grateful to Karine Leblanc for the LC/MS assistance, and Jean-Christophe Jullian, Jean-François Gallard and Camille Dejean for NMR assistance.

Keywords: Alkaloids, Apocynaceae, networking, mass, Geissospermum, Pleiocarpa, Picralima.

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